Schedule H1

Oral

Tablets: 100 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

▶ Drug-Resistant Tuberculosis (MDR-TB / Pre-XDR-TB / XDR-TB) — Adults

Must be used as part of WHO-recommended combination regimen under NTEP/PMDT framework

Parameter Dosing Details

Starting dose 400 mg once daily with food for 14 days (loading phase)

Titration Reduce to 200 mg three times weekly from week 3 (at least 48 hours between doses)

Usual maintenance dose 200 mg three times weekly (e.g., Monday-Wednesday-Friday)

Maximum dose 400 mg/day (loading phase only); 200 mg per dose (maintenance phase)

Total duration 24 weeks (may be extended in individualized regimens under specialist guidance)

Key Clinical Notes:

• Must always be combined with at least 3–4 other effective anti-TB agents

• Monotherapy is strictly contraindicated due to rapid resistance development

• Take with food to enhance absorption

• ECG monitoring mandatory due to QTc prolongation risk

• Only to be prescribed within NTEP DR-TB framework at designated centres

▶ Drug-Resistant Tuberculosis — BPaL/BPaLM Regimen (Shorter Regimen)

For eligible patients under NTEP-approved shorter MDR-TB regimens

Parameter Dosing Details

Starting dose 400 mg once daily with food for 14 days

Titration 200 mg three times weekly from week 3

Usual maintenance dose 200 mg three times weekly

Duration 24–26 weeks as part of BPaL/BPaLM regimen

• Patient eligibility determined by NTEP criteria

• Combined with pretomanid, linezolid ± moxifloxacin

Secondary Indications — Adults (Off-label, if any)

Not applicable.

No established off-label uses documented in Indian practice. Use is strictly limited to DR-TB within supervised NTEP/PMDT regimens.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

▶ Drug-Resistant Tuberculosis (RR-TB / MDR-TB / XDR-TB) — Children

Only under specialist supervision at designated NTEP DR-TB centres

Weight-Based Dosing Table:

Weight Band Loading Phase (Weeks 1–2) Maintenance Phase (Weeks 3–24)

15 kg to <23 kg 200 mg once daily 100 mg three times weekly

23 kg to <30 kg 200 mg once daily 100 mg three times weekly

≥30 kg 400 mg once daily 200 mg three times weekly

Key Clinical Notes:

• Minimum age: 5 years

• Minimum weight: 15 kg

• Children <5 years or <15 kg: Use only under exceptional circumstances at specialized NTEP centres with close monitoring

• Administer with food

• Total duration: 24 weeks (may extend based on regimen)

Mandatory Monitoring in Paediatrics:

• ECG (QTc interval) at baseline, weekly for first month, then monthly

• Serum electrolytes (K⁺, Mg²⁺, Ca²⁺) at baseline and periodically

• Liver function tests every 2–4 weeks

• Growth monitoring

Secondary Indications — Paediatric Doses (Off-label, if any)

Not applicable.

Mild to moderate impairment No dose adjustment required

• Known hypersensitivity to bedaquiline or any excipient

• Baseline QTc interval >500 ms

• History of torsades de pointes or symptomatic ventricular arrhythmias

• Concomitant use with strong CYP3A4 inducers (e.g., rifampicin, rifabutin) — significantly reduces bedaquiline levels

• Baseline QTc interval >450 ms — increased risk of arrhythmia; intensive ECG monitoring required

• Pre-existing cardiac disease (heart failure, bradyarrhythmias, coronary artery disease)

• Electrolyte abnormalities (hypokalaemia, hypomagnesaemia, hypocalcaemia) — correct before initiation

• Hepatic dysfunction — risk of drug-induced liver injury

• Concurrent use of other QT-prolonging drugs (moxifloxacin, clofazimine, fluoroquinolones)

• HIV co-infection on antiretroviral therapy — potential drug interactions

• Alcohol use disorder — increased hepatotoxicity risk

• Hypoalbuminaemia — may affect drug distribution

Parameter Detail

Safety Limited human data; animal studies indicate potential risk (skeletal variations)

Use in pregnancy Use only if no safer alternative available for DR-TB; benefit must clearly outweigh risk

Preferred alternatives Consult DR-TB specialist — regimen individualization required; linezolid-based regimens may be considered under guidance

Monitoring Maternal ECG and LFT monitoring; fetal growth surveillance; obstetric consultation essential

Parameter Detail

Compatibility Not recommended — insufficient human data on excretion

Milk levels Unknown; long half-life suggests potential accumulation

Preferred alternatives Formula feeding recommended during therapy by most PMDT centres

Infant monitoring If breastfeeding unavoidable: monitor infant for jaundice, feeding difficulties, cardiac symptoms

• Starting dose: Standard adult dosing (400 mg daily for 2 weeks, then 200 mg three times weekly)

• Titration: No specific adjustment, but slower dose escalation may be considered if tolerability concerns

• Special considerations:

• Limited safety data in patients >65 years

• Higher risk of QT prolongation — baseline and frequent ECG monitoring essential

• Reduced hepatic clearance possible — monitor LFTs more frequently

• Assess cardiac, renal, and hepatic function before initiation

• Monitor for drug interactions with concomitant medications

Interacting Drug Effect/Risk Recommendation

Rifampicin, Rifabutin Marked reduction in bedaquiline exposure via strong CYP3A4 induction Contraindicated — avoid co-administration

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, lopinavir) Significantly increased bedaquiline levels; heightened QT and hepatotoxicity risk Avoid; if essential, limit duration to 14 days maximum and monitor closely

Moxifloxacin Additive QT prolongation Intensive ECG monitoring mandatory; use together only if essential

Clofazimine Additive QT prolongation Monitor QTc closely; consider alternative if QTc prolongation occurs

Delamanid Additive QT prolongation (both drugs prolong QT) Use together only under specialist supervision with weekly ECG and cardiology input

Haloperidol, Ondansetron QT prolongation risk Avoid or use with ECG monitoring

Interacting Drug Effect/Risk Recommendation

Efavirenz Decreased bedaquiline exposure via CYP3A4 induction Avoid if possible; if used, close monitoring for efficacy

Clarithromycin, Erythromycin Moderate CYP3A4 inhibition; potential increased bedaquiline levels Monitor QTc if co-administered

Fluconazole Moderate CYP3A4 inhibition; QT prolongation risk ECG monitoring advised

Other hepatotoxic TB drugs (pyrazinamide, ethionamide, prothionamide) Cumulative hepatotoxicity risk Monitor LFTs more frequently

Alcohol Increased hepatotoxicity risk Advise avoidance throughout treatment

Levofloxacin Potential additive QT effect Monitor ECG

• Nausea

• Arthralgia

• Headache

• Elevated hepatic transaminases (ALT, AST)

• Dizziness

• Anorexia

• Vomiting

• Chest pain

• QTc prolongation (dose-related, often asymptomatic)

Adverse Effect Clinical Note

QTc prolongation / Torsades de pointes Discontinue if QTc >500 ms or increase >60 ms from baseline; correct electrolytes; cardiology consultation

Severe hepatotoxicity Discontinue if ALT/AST >5× ULN or if symptomatic (jaundice, abdominal pain, coagulopathy)

Unexplained syncope or palpitations May indicate arrhythmia — urgent ECG and evaluation required

Increased mortality signal Higher mortality observed in clinical trials vs placebo (cause unclear) — use only under strict NTEP protocols

After initiation ECG weekly for first 4 weeks, then monthly; LFTs every 2–4 weeks during initial phase

During treatment Serum electrolytes monthly (more frequently if abnormal); clinical assessment for cardiac symptoms; sputum monitoring for culture conversion

Long-term Periodic ECG throughout 24-week course; adherence counselling at each visit; post-treatment cardiac follow-up if QTc prolongation noted

• Sirturo (Janssen Pharmaceuticals) — supplied primarily through NTEP under conditional access

• Bedaquiline (generic) — available through select NTEP DR-TB centres

Not freely available in private retail market; distribution controlled through government programme

Supply Channel Approximate Cost

Government supply (NTEP/PMDT) Free of cost at designated DR-TB centres

Private procurement (exceptional cases) Approximately ₹11,000–15,000 per 24-week regimen

• Not included in NLEM 2022

• Private market availability extremely limited

• Prescription and dispensing restricted to NTEP-approved centres

1. Never use as monotherapy: Bedaquiline must always be part of a multi-drug DR-TB regimen to prevent emergence of resistance.

1. QTc monitoring is non-negotiable: Obtain baseline ECG and ensure QTc <450 ms before initiation; repeat weekly for first month, then monthly.

1. Correct electrolytes first: Hypokalaemia, hypomagnesaemia, and hypocalcaemia must be corrected before starting and monitored throughout therapy.

1. Avoid rifampicin co-administration: Rifampicin dramatically reduces bedaquiline levels — these drugs are incompatible in the same regimen.

1. Food enhances absorption: Administer with food to improve bioavailability; fasting reduces drug exposure.

1. Bedaquiline + Delamanid combination: If both are required, weekly ECG monitoring with cardiology input is mandatory due to additive QT effects.

1. Long half-life implications: Terminal half-life is approximately 5–6 months; adverse effects may persist after discontinuation; inform patients accordingly.

bedaquiline; MDR-TB; XDR-TB; BPaL; drug-resistant-TB; QT-prolongation; NTEP; PMDT; antimycobacterial; hepatotoxicity; cardiotoxicity

RxIndia v1.0 — 21 Jun 2025

• CDSCO approved product information

• NTEP India PMDT Guidelines (2021, 2023)

• WHO Consolidated Guidelines on Drug-Resistant TB Treatment (2022)

• ICMR Guidance on Drug-Resistant TB Management

• AIIMS Nodal DR-TB Centre Protocols

• Indian Pharmacopoeia / NFI 2021

• Janssen Pharmaceuticals — Bedaquiline product monograph

• Goodman & Gilman's Pharmacological Basis of Therapeutics